文献类型： 外文期刊

作者： Li, Yingying ¹ ; Li, Junqi ² ; Jia, Dan ¹ ; Gao, Shandian ¹ ; Guo, Yanan ³ ; Liu, Junlong ¹ ; Wang, Jinming ¹ ; Guan, Guiquan ¹ ; Luo, Jianxun ¹ ; Yin, Hong ¹ ; Xiao, Sa ² ; Li, Youquan ¹ ;

作者机构： 1.Chinese Acad Agr Sci, Lanzhou Vet Res Inst, State Key Lab Anim Dis Control & Prevent, Key Lab Vet Parasitol Gansu Prov, Lanzhou, Gansu, Peoples R China

2.Northwest A&F Univ, Coll Vet Med, Yangling, Shaanxi, Peoples R China

3.Ningxia Acad Agr & Forestry Sci, Inst Anim Sci, Yinchuan, Ningxia, Peoples R China

4.Yangzhou Univ, Jiangsu Coinnovat Ctr Prevent & Control Important, Ctr Prevent & Control Important Anim Infect Dis &, Yangzhou, Jiangsu, Peoples R China

5.Guangdong Ocean Univ, Coll Coastal Agr Sci, Dept Vet Med, Zhanjiang, Guangdong, Peoples R China

6.Chinese Acad Agr Sci, Lanzhou Vet Res Inst, State Key Lab Anim Dis Control & Prevent, Key Lab Veterinary Parasitol Gansu Prov, Adm Off 401,Xujiaping 1, Gansu, France

期刊名称：JOURNAL OF IMMUNOLOGY （ 影响因子：4.4； 五年影响因子：5.2 ）

ISSN： 0022-1767

年卷期： 2024 年 212 卷 1 期

页码：

收录情况： SCI

摘要： Salmonella enterica serovar Typhimurium (S. Tm) causes severe foodborne diseases. Interestingly, gut microbial tryptophan (Trp) metabolism plays a pivotal role in such infections by a yet unknown mechanism. This study aimed to explore the impact of Trp metabolism on S. Tm infection and the possible mechanisms involved. S. Tm-infected C57BL6/J mice were used to demonstrate the therapeutic benefits of the Bacillus velezensis JT3-1 (B. velezensis/JT3-1) strain or its cell -free supernatant in enhancing Trp metabolism. Targeted Trp metabolomic analyses indicated the predominance of indole-3-lactic acid (ILA), an indole derivative and ligand for aryl hydrocarbon receptor (AHR). Based on the 16S amplicon sequencing and correlation analysis of metabolites, we found that B. velezensis supported the relative abundance of Lactobacillus and Ligilactobacillus in mouse gut and showed positive correlations with ILA levels. Moreover, AHR and its downstream genes (especially IL -22) significantly increased in mouse colons after B. velezensis or cell -free supernatant treatment, suggesting the importance of AHR pathway activation. In addition, ILA was found to stimulate primary mouse macrophages to secrete IL -22, which was antagonized by CH -223191. Furthermore, ILA could protect mice from S. Tm infection by increasing IL -22 in Ahr+/- mice, but not in Ahr-/- mice. Finally, Trp-rich feeding showed amelioration of S. Tm infection in mice, and the effect depended on gut microbiota. Taken together, these results suggest that B. velezensis-associated ILA contributes to protecting mice against S. Tm infection by activating the AHR/IL-22 pathway. This study provides insights into the involvement of microbiota-derived Trp catabolites in protecting against Salmonella infection. The Journal of Immunology, 2024,212: 57-68.